Anteriorization of CRABP-I expression by retinoic acid in the developing mouse central nervous system and its relationship to teratogenesis

Dev Biol. 1995 Apr;168(2):514-28. doi: 10.1006/dbio.1995.1099.

Abstract

We have investigated the role that cellular retinoic acid binding protein I (CRABP-I) may play in the development of the murine hindbrain. Since the central nervous system (CNS) represents a major site of the teratogenic action of retinoic acid (RA), we have also determined the effects of exposure of high levels of RA on CRABP-I expression within the CNS. Expression of CRABP-I can first be detected within the presumptive hindbrain of presomitic mouse embryos and later also appears in neural crest cells and neural crest derivatives; it is thus tissue specific at these early stages. Exposure of 7.75-day mouse embryos to RA induces two phenotypes: one is externally normal and the other is exencephalic. In the exencephalic embryos we show that there is abnormal crest migration, a fusion of the trigeminal and facial-acoustic ganglia, a rostral and lateral shift of the otic vesicle, and a loss of hindbrain rhombomeres. Furthermore, and in contrast to in vitro studies, we demonstrate that CRABP-I appears to be up-regulated in both phenotypes of mouse embryos treated with RA and that this up-regulation is accompanied by an anteriorization of its expression within the nervous system. This new CRABP-I expression domain thus retains its tissue specificity. The role that CRABP-I may play in normal development of the hindbrain and in teratogenesis and the similarity of these results to those obtained with various Hox genes are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / embryology*
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology
  • Embryonic and Fetal Development
  • Mice
  • RNA, Messenger / analysis
  • Receptors, Retinoic Acid / biosynthesis*
  • Teratoma / etiology
  • Tretinoin / adverse effects
  • Tretinoin / pharmacology*
  • Up-Regulation

Substances

  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Tretinoin